{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T04:17:17Z","timestamp":1772770637585,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Immune checkpoint inhibitor (ICI)\u2010based treatment regimens have become the standard of care for first\u2010line treatment of metastatic epidermal growth factor receptor (EGFR)\/anaplastic lymphoma kinase (ALK) wild\u2010type non\u2010small cell lung cancer (NSCLC). Nevertheless, most patients inevitably develop disease progression, and the mechanisms of resistance to first\u2010line immunotherapy are not clear. ICIs in combination with agents targeting other pathways may serve as second\u2010line therapy options. Plinabulin is a selective immunomodulating microtubule\u2010binding agent which inhibits the polymerization of tubulin monomers, with multiple mechanisms to inhibit tumor growth. Clinical studies have demonstrated preliminary the antitumor efficacy of this agent. Therefore, we hypothesize that a combination of plinabulin with programmed death 1 (PD\u20101) inhibitor and docetaxel may result in higher efficacy and fewer side effects leading to better tolerance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this investigator\u2010initiated, single\u2010arm, open\u2010label, phase II trial, metastatic NSCLC patients who acquired resistance to first\u2010line immunotherapy\u2010based therapy will be enrolled. Participants will receive pembrolizumab 200\u2009mg D1, plinabulin 30\u2009mg\/m<jats:sup>2<\/jats:sup> D1 and D8, and docetaxel 75\u2009mg\/m<jats:sup>2<\/jats:sup> D1 intravenously for a 21\u2010day\u2009cycle. The study intervention will be given until disease progression, intolerable toxicity, informed consent withdrawal or investigator decision. The primary endpoint is investigator\u2010based objective response rate per Response Evaluation Criteria in Solid Tumors, version 1.1. The secondary endpoints are progression\u2010free survival, overall survival, duration of response, and safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This trial will provide evidence of the benefit and safety of pembrolizumab in combination with plinabulin and docetaxel in metastatic NSCLC patients who have been exposed and developed resistance to first\u2010line PD\u20101\/PD\u2010L1 inhibitor either as monotherapy or in combination with chemotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.14806","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T04:03:16Z","timestamp":1675310596000},"page":"773-778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Study protocol of <scp>KeyPemls<\/scp>\u2010004: A phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non\u2010small cell lung cancer and progressive disease (<scp>PD<\/scp>) after immunotherapy (<scp>PD<\/scp>\u20101\/<scp>PD\u2010L1<\/scp> inhibitor) alone or in combination with platinum\u2010doublet chemotherapy"],"prefix":"10.1111","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0490-5109","authenticated-orcid":false,"given":"Jia","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4040-6115","authenticated-orcid":false,"given":"Minjiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxing","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruili","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2832-2664","authenticated-orcid":false,"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengzhao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2014.221"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1514296"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606774"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801005"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1810865"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32409-7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0142-8"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.01.017"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.07.017"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.12.2354"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2004.08.163"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2019.08.022"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.08.057"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-019-03998-w"},{"issue":"1326","key":"e_1_2_7_17_1","article-title":"LBA48 DUBLIN\u20103 (BPI\u20102358\u2010103): a global phase (Ph) III trial with the plinabulin\/docetaxel (Plin\/Doc) combination vs. Doc in 2nd\/3rd line NSCLC patients (pts) with EGFR\u2010wild type (wt) progressing on a prior platinum\u2010based regimen","volume":"32","author":"Han B","year":"2021","journal-title":"Ann Oncol"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.8570"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2019.12.017"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34565"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-21-3646"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.01.052"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.644608"}],"container-title":["Thoracic Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1759-7714.14806","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1759-7714.14806","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1759-7714.14806","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T23:19:31Z","timestamp":1692659971000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1759-7714.14806"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2]]},"references-count":22,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1111\/1759-7714.14806"],"URL":"https:\/\/doi.org\/10.1111\/1759-7714.14806","archive":["Portico"],"relation":{},"ISSN":["1759-7706","1759-7714"],"issn-type":[{"value":"1759-7706","type":"print"},{"value":"1759-7714","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2]]},"assertion":[{"value":"2023-01-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}